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Translational Research: the Journal of Laboratory and Clinical Medicine

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https://www.readbyqxmd.com/read/28081931/neurogenin-2-transduced-human-neural-progenitor-cells-attenuate-neonatal-hypoxic-ischemic-brain-injury
#1
Il-Shin Lee, Kyo Yeon Koo, Kwangsoo Jung, Miri Kim, Il-Sun Kim, Kyujin Hwang, Seokhwan Yun, Haejin Lee, Jeong Eun Shin, Kook In Park
Neonatal hypoxic-ischemic (HI) brain injury leads to high mortality and neurodevelopmental disabilities. Multipotent neural progenitor cells (NPCs) with self-renewing capacity have the potential to reduce neuronal loss and improve the compromised environment in the HI brain injury. However, the therapeutic efficacy of neuronal-committed progenitor cells and the underlying mechanisms of recovery are not yet fully understood. Therefore, this study investigated the regenerative ability and action mechanisms of neuronally committed human NPCs (hNPCs) transduced with neurogenin-2 (NEUROG2) in neonatal HI brain injury...
December 29, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28087261/dna-aptamer-probes-for-detection-of-estrogen-receptor-%C3%AE-positive-carcinomas
#2
Arghya Sett, Bibhuti Bhusan Borthakur, Jagannath Dev Sharma, Amal Chandra Kataki, Utpal Bora
Estrogen receptor alpha (ERα) which is a ligand-activated transcription factor also known as NR3A1 (nuclear receptor subfamily 3, group A, member 1). It is an important biomarker for breast cancer metastasis. In the present study, we report a novel DNA aptamer candidate against estrogen receptor (ER) alpha structure. The enriched aptamer candidate was obtained after 14 iterative cycles of in vitro protein-SELEX process. Isothermal calorimetry study suggests the nanomolar sensitivity of the candidate ER_Apt1 to its target protein...
December 25, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28068521/hiv-and-its-relationship-to-insulin-resistance-and-lipid-abnormalities
#3
REVIEW
Lemuel R Non, Gerome V Escota, William G Powderly
Antiretroviral therapy has revolutionized the care of people with human immunodeficiency virus (HIV) by reducing morbidity and mortality from acquired immunodeficiency syndrome-related conditions. Despite longer life expectancy, however, HIV-infected individuals continue to have a higher risk of death compared with the general population. This has been attributed to the increasing incidence of noncommunicable diseases, in particular, atherosclerotic cardiovascular diseases. This is driven, in part, by the emergence of metabolic disorders, particularly dyslipidemia, insulin resistance, and lipodystrophy, in those on antiretroviral therapy...
December 23, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28056336/the-clinical-role-of-circulating-free-tumor-dna-in-gastrointestinal-malignancy
#4
REVIEW
Jessica A Howell, Shahid A Khan, Susanne Knapp, Mark R Thursz, Rohini Sharma
Circulating cell-free DNA (cfDNA) is DNA released from necrotic or apoptotic cells into the bloodstream. While both healthy cells and cancer cells release cfDNA, tumors are associated with higher levels of tumor-derived circulating cell-free DNA (ctDNA) detectable in blood. Absolute levels of ctDNA and its genetic mutations and epigenetic changes show promise as potentially useful biomarkers of tumor biology, progression, and response to therapy. Moreover, studies have demonstrated the discriminative accuracy of ctDNA levels for diagnosis of gastrointestinal cancer compared with benign inflammatory diseases...
December 22, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28034761/bile-acid-receptor-tgr5-overexpression-is-associated-with-decreased-intestinal-mucosal-injury-and-epithelial-cell-proliferation-in-obstructive-jaundice
#5
Chen-Guang Ji, Xiao-Li Xie, Jie Yin, Wei Qi, Lei Chen, Yun Bai, Na Wang, Dong-Qiang Zhao, Xiao-Yu Jiang, Hui-Qing Jiang
Bile acids stimulate intestinal epithelial proliferation in vitro. We sought to investigate the role of the bile acid receptor TGR5 in the protection of intestinal epithelial proliferation in obstructive jaundice. Intestinal tissues and serum samples were obtained from patients with malignant obstructive jaundice and from bile duct ligation (BDL) rats. Intestinal permeability and morphological changes in the intestinal mucosa were observed. The functions of TGR5 in cell proliferation in intestinal epithelial injury were determined by overexpression or knockdown studies in Caco-2 and FHs 74 Int cells pretreated with lipopolysaccharide (LPS)...
December 18, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28034760/insulin-resistance-in-alzheimer-s-disease
#6
REVIEW
Thomas Diehl, Roger Mullins, Dimitrios Kapogiannis
The links between systemic insulin resistance (IR), brain-specific IR, and Alzheimer's disease (AD) has been an extremely productive area of current research. This review will cover the fundamentals and pathways leading to IR, its connection to AD via cellular mechanisms, the most prominent methods and models used to examine it, an introduction to the role of extracellular vesicles (EVs) as a source of biomarkers for IR and AD, and an overview of modern clinical studies on the subject. To provide additional context, we also present a novel analysis of the spatial correlation of gene expression in the brain with the aid of Allen Human Brain Atlas data...
December 13, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28034759/targeting-p-selectin-glycoprotein-ligand-1-p-selectin-interactions-as-a-novel-therapy-for-metabolic-syndrome
#7
REVIEW
Madhukar S Patel, David Miranda-Nieves, Jiaxuan Chen, Carolyn A Haller, Elliot L Chaikof
Obesity-induced insulin resistance and metabolic syndrome continue to pose an important public health challenge worldwide as they significantly increase the risk of type 2 diabetes and atherosclerotic cardiovascular disease. Advances in the pathophysiologic understanding of this process has identified that chronic inflammation plays a pivotal role. In this regard, given that both animal models and human studies have demonstrated that the interaction of P-selectin glycoprotein ligand-1 (PSGL-1) with P-selectin is not only critical for normal immune response but also is upregulated in the setting of metabolic syndrome, PSGL-1/P-selectin interactions provide a novel target for preventing and treating resultant disease...
December 9, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28027930/tocilizumab-improves-the-proatherothrombotic-profile-of-rheumatoid-arthritis-patients-modulating-endothelial-dysfunction-netosis-and-inflammation
#8
P Ruiz-Limón, R Ortega, I Arias de la Rosa, M C Abalos-Aguilera, C Perez Sanchez, Y Jimenez Gomez, E Peralbo-Santaella, P Font, D Ruiz-Vilches, G Ferrin, E Collantes-Estevez, A Escudero, C H López Pedrera, N Barbarroja
Tocilizumab (TCZ) is an effective treatment for rheumatoid arthritis (RA). However, the changes that occurred after TCZ therapy on endothelial dysfunction, monocyte activity, NETosis, and oxidative stress, the principal effectors of atherosclerosis and cardiovascular disease, have not been analyzed yet. A total of 20 RA patients received 162 mg per week subcutaneous TCZ for 6 months. Endothelial function was measured through postocclusive hyperemia using Laser Doppler. Oxidative stress markers in monocytes and neutrophils were analyzed by flow cytometry...
December 9, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28027929/nrf2-exerts-cell-autonomous-antifibrotic-effects-compromised-function-in-systemic-sclerosis-and-therapeutic-rescue-with-a-novel-heterocyclic-chalcone-derivative
#9
Jun Wei, Hongyan Zhu, Gabriel Lord, Mitra Bhattachayya, Brielle M Jones, Graham Allaway, Shyam S Biswal, Benjamin Korman, Roberta G Marangoni, Warren G Tourtellotte, John Varga
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) governs antioxidant, innate immune and cytoprotective responses and its deregulation is prominent in chronic inflammatory conditions. To examine the hypothesis that Nrf2 might be implicated in systemic sclerosis (SSc), we investigated its expression, activity, and mechanism of action in SSc patient samples and mouse models of fibrosis and evaluated the effects of a novel pharmacologic Nrf2 agonist. We found that both expression and activity of Nrf2 were significantly reduced in SSc patient skin biopsies and showed negative correlation with inflammatory gene expression...
December 9, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28025032/the-metabolic-syndrome-and-chronic-kidney-disease
#10
REVIEW
Xin Zhang, Lilach O Lerman
The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including insulin resistance (IR), dyslipidemia, and hypertension, which may also foster development of chronic kidney disease. The mechanisms of MetS-induced kidney disease are not fully understood. The purpose of this review is to summarize recent discoveries regarding the impact of MetS on the kidney, particularly on the renal microvasculature and cellular mitochondria. Fundamental manifestations of MetS include IR and adipose tissue expansion, the latter promoting chronic inflammation and oxidative stress that exacerbate IR...
December 9, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28011152/adenosine-a2a-receptor-stimulation-blocks-development-of-nonalcoholic-steatohepatitis-in-mice-by-multilevel-inhibition-of-signals-that-cause-immunolipotoxicity
#11
Elisa Alchera, Simona Rolla, Chiara Imarisio, Valentina Bardina, Guido Valente, Francesco Novelli, Rita Carini
Lipotoxicity and immunoinflammation are associated with the evolution of steatosis toward nonalcoholic steatohepatitis (NASH). This study reports the ability of adenosine A2a receptor (A2aR) activation to inhibit NASH development by modulating the responses of CD4(+) T-helper (Th) cells to avoid an immuno-mediated potentiation of lipotoxicity. The effect of the A2aR agonist CGS21680 on immunoinflammatory signals, CD4(+)Th cell infiltration and immunolipotoxicity was analyzed in steatotic C57BL/6 mice fed with a methionine-choline-deficient (MCD) diet and in mouse hepatocytes exposed to palmitic acid (PA)...
December 6, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27986604/cell-therapy-for-the-degenerating-intervertebral-disc
#12
REVIEW
Wei Tong, Zhouyu Lu, Ling Qin, Robert L Mauck, Harvey E Smith, Lachlan J Smith, Neil R Malhotra, Martin F Heyworth, Franklin Caldera, Motomi Enomoto-Iwamoto, Yejia Zhang
Spinal conditions related to intervertebral disc (IVD) degeneration cost billions of dollars in the US annually. Despite the prevalence and soaring cost, there is no specific treatment that restores the physiological function of the diseased IVD. Thus, it is vital to develop new treatment strategies to repair the degenerating IVD. Persons with IVD degeneration without back pain or radicular leg pain often do not require any intervention. Only patients with severe back pain related to the IVD degeneration or biomechanical instability are likely candidates for cell therapy...
November 28, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27931982/jak-inhibitor-tofacitinib-suppresses-interferon-alfa-production-by-plasmacytoid-dendritic-cells-and-inhibits-arthrogenic-and-antiviral-effects-of-interferon-alfa
#13
Patrick P C Boor, Petra E de Ruiter, Patrick S Asmawidjaja, Erik Lubberts, Luc J W van der Laan, Jaap Kwekkeboom
Tofacitinib is an oral Janus kinase inhibitor that is effective for the treatment of rheumatoid arthritis and shows encouraging therapeutic effects in several other autoimmune diseases. A prominent adverse effect of tofacitinib therapy is the increased risk of viral infections. Despite its advanced stage of clinical development, the modes of action that mediate the beneficial and adverse effects of tofacitinib in autoimmune diseases remain unclear. Interferon alfa (IFNα) produced by plasmacytoid dendritic cells (PDCs) is critically involved in the pathogenesis of many systemic autoimmune diseases and in immunity to viral infections...
November 20, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27914223/osteogenesis-imperfecta-new-genes-reveal-novel-mechanisms-in-bone-dysplasia
#14
REVIEW
Heeseog Kang, Smriti Aryal A C, Joan C Marini
Osteogenesis imperfecta (OI) is a skeletal dysplasia characterized by fragile bones and short stature and known for its clinical and genetic heterogeneity which is now understood as a collagen-related disorder. During the last decade, research has made remarkable progress in identifying new OI-causing genes and beginning to understand the intertwined molecular and biochemical mechanisms of their gene products. Most cases of OI have dominant inheritance. Each new gene for recessive OI, and a recently identified gene for X-linked OI, has shed new light on its (often previously unsuspected) function in bone biology...
November 19, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27908750/mesenchymal-stromal-cell-based-therapies-reduce-obesity-and-metabolic-syndromes-induced-by-a-high-fat-diet
#15
Chien-Wei Lee, Wei-Ting Hsiao, Oscar Kuang-Sheng Lee
Obesity is an alarming global health problem that results in multiaspect metabolic syndromes in both genders and most age groups. The lack of effective therapies for obesity and its associated metabolic syndrome is an urgent societal issue. To elucidate whether mesenchymal stromal cell (MSC)-based therapies can ameliorate high-fat diet-induced obesity and compare the effectiveness of several methodological approaches, we transplanted human MSCs, MSC-derived brown adipocytes (M-BA), and MSC lysateinto obese mice...
November 12, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27893988/endothelin-signaling-in-bone
#16
REVIEW
Jasmin Kristianto, Michael G Johnson, Rafia Afzal, Robert D Blank
The endothelin (ET) system includes 3 small peptide hormones and a pair of G protein-coupled receptors. All 3 ETs are secreted as biologically inert precursors that must be activated by proteolytic cleavage after secretion. This reaction can be catalyzed by a pair of specific, membrane-bound extracellular ET converting enzymes or by nonspecific tissue proteases. The ET1/EDNRA axis is essential in development, with knockout mice for either displaying a similar phenotype featuring multiple defects of the craniofacial skeleton and cardiac outflow tract...
November 11, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27893987/transdisciplinary-approaches-enhance-the-production-of-translational-knowledge
#17
REVIEW
Timothy H Ciesielski, Melinda C Aldrich, Carmen J Marsit, Robert A Hiatt, Scott M Williams
The primary goal of translational research is to generate and apply knowledge that can improve human health. Although research conducted within the confines of a single discipline has helped us to achieve this goal in many settings, this unidisciplinary approach may not be optimal when disease causation is complex and health decisions are pressing. To address these issues, we suggest that transdisciplinary approaches can facilitate the progress of translational research, and we review publications that demonstrate what these approaches can look like...
November 10, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27886976/airway-and-serum-adipokines-after-allergen-and-diesel-exposure-in-a-controlled-human-crossover-study-of-atopic-adults
#18
Marabeth M Kramer, Jeremy A Hirota, Akshay Sood, Kay Teschke, Christopher Carlsten
Adipokines are mediators released from adipose tissue. These proteins are regarded as active elements of systemic and pulmonary inflammation, whose dysregulation can alter an individual's risk of developing allergic lung diseases. Despite this knowledge, adipokine responses to inhaled stimuli are poorly understood. We sought to measure serum and lung adiponectin, leptin, and resistin in an atopic adult study population following exposure to allergen and diesel exhaust (DE). Two types of lung samples including bronchoalveolar lavage (BAL) and bronchial wash (BW), and a time course of serum samples, were collected from the 18 subjects who participated in the randomized, double-blinded controlled human study...
November 9, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27842222/molecular-imaging-of-the-kidney-in-lupus-nephritis-to-characterize-response-to-treatment
#19
Samir V Parikh, Ana Malvar, Huijuan Song, Valeria Alberton, Bruno Lococo, Jay Vance, Jianying Zhang, Lianbo Yu, Dan Birmingham, Brad H Rovin
The consequences of treatment for the kidney at the molecular level have not been explored in human lupus nephritis (LN). In this investigation, changes in intrarenal transcript expression were measured and correlated with response in a LN cohort that underwent serial kidney biopsies. The intrarenal transcript expression of 19 patients with proliferative LN (Class III or IV) was measured at diagnostic biopsy (Bx1) and after induction therapy was completed (Bx2) using Nanostring technology. Patients were segregated by clinical response into complete responders (n = 5, CR) or nonresponders (n = 4, NR)...
November 1, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/27855281/car-t-therapy-for-leukemia-progress-and-challenges
#20
REVIEW
Xin Wang, Qing Xiao, Zhe Wang, Wen-Li Feng
Despite the rapid development of therapeutic strategies, leukemia remains a type of difficult-to-treat hematopoietic malignancy that necessitates introduction of more effective treatment options to improve life expectancy and quality of patients. Genetic engineering in adoptively transferred T cells to express antigen-specific chimeric antigen receptors (CARs) has proved highly powerful and efficacious in inducing sustained responses in patients with refractory malignancies, as exemplified by the success of CD19-targeting CAR-T treatment in patients with relapsed acute lymphoblastic leukemia...
October 27, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
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